Methods and systems for endobronchial diagnostics

ABSTRACT

Methods and systems for targeting, accessing and diagnosing diseased lung compartments are disclosed. The method comprises introducing a diagnostic catheter with an occluding member at its distal end into a lung segment via an assisted ventilation device; inflating the occluding member to isolate the lung segment; and performing a diagnostic procedure with the catheter while the patient is ventilated. The proximal end of the diagnostic catheter is configured to be attached to a console. The method may also comprise introducing the diagnostic catheter into the lung segment; inflating the occluding member to isolate the lung segment; and monitoring blood oxygen saturation. The method may further comprise introducing the diagnostic catheter into the lung segment; determining tidal flow volume in the lung segment; determining total lung capacity of the patient; and determining a flow rank value based on the tidal flow volume of the lung segment and the total lung capacity.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a continuation of U.S. patent applicationSer. No. 16/107,849, filed Aug. 21, 2018, now U.S. Pat. No. 10,932,706,which is a divisional of U.S. patent application Ser. No. 14/339,197,filed Jul. 23, 2014, now U.S. Pat. No. 10,076,271, which is a divisionalof U.S. patent application Ser. No. 13/174,633), filed Jun. 30, 2011,now U.S. Pat. No. 8,808,194, which claims priority under 35 U.S.C.Section 119(e) to U.S. Provisional Patent Application Ser. No.61/360,811, filed Jul. 1, 2010, the full disclosures of which are herebyincorporated by reference.

BACKGROUND OF THE INVENTION 1. Field of the Invention

This invention relates generally to methods for diagnosis and treatmentof lung disease.

2. Description of the Related Art

Chronic obstructive pulmonary disease (COPD), including emphysema andchronic bronchitis, is a significant medical problem currently affectingaround 16 million people in the U.S. alone (about 6% of the U.S.population). In general, two types of diagnostic tests are performed ona patient to determine the extent and severity of COPD: 1) imagingtests; and 2) functional tests. Imaging tests, such as chest x-rays,computerized tomography (CT) scans, Magnetic Resonance Imaging (MRI)images, perfusion scans, and bronchograms, provide a good indicator ofthe location, homogeneity and progression of the diseased tissue.However, imaging tests do not provide a direct indication of how thedisease is affecting the patient's overall lung function andrespiration. Lung function can be better assessed using functionaltesting, such as spirometry, plethysmography, oxygen saturation, andoxygen consumption stress testing, among others. Together, these imagingand functional diagnostic tests are used to determine the course oftreatment for the patient.

One of the emerging treatments for COPD involves the endoscopicintroduction of endobronchial occluders or one-way valve devices(“endobronchial valves” or “EBVs”) into pulmonary passageways to reducethe volume of one or more hyperinflated lung compartments, thus allowinghealthier compartments more room to breathe and perhaps reducingpressure on the heart. Examples of such a method and implant aredescribed, for example, in U.S. patent application Ser. No. 11/682,986and U.S. Pat. No. 7,798,147, the full disclosures of which are herebyincorporated by reference. One-way valves implanted in airways leadingto a lung compartment restrict air flow in the inhalation direction andallow air to flow out of the lung compartment upon exhalation, thuscausing the adjoining lung compartment to collapse over time. Occludersblock both inhalation and exhalation, also causing lung collapse overtime.

It has been suggested that the use of endobronchial implants for lungvolume reduction might be most effective when applied to lungcompartments which are not affected by collateral ventilation.Collateral ventilation occurs when air passes from one lung compartmentto another through a collateral channel rather than the primary airwaychannels. If collateral airflow channels are present in a lungcompartment, implanting a one-way valve or occluder might not be aseffective, because the compartment might continue to fill with air fromthe collateral source and thus fail to collapse as intended. In manycases, COPD manifests itself in the formation of a large number ofcollateral channels caused by rupture of alveoli due to hyperinflation,or by destruction and weakening of alveolar tissue.

An endobronchial catheter-based diagnostic system typically used forcollateral ventilation measurement is disclosed in U.S. PatentPublication No. 2003/0051733 (hereby incorporated by reference), whereinthe catheter uses an occlusion member to isolate a lung segment and theinstrumentation is used to gather data such as changes in pressure andvolume of inhaled/exhaled air. Current state of the art methods forcollateral ventilation measurement are disclosed in U.S. Pat. No.7,883,471 and U.S. Patent Publication Nos. 2008/0027343 and 2007/0142742(all of which are hereby incorporated by reference), in which anisolation catheter is used to isolate a target lung compartment andpressure changes therein are sensed to detect the extent of collateralventilation. The applications also disclose measurement of gasconcentrations to determine the efficiency of gas exchange within thelung compartment. Similar methods are disclosed in PCT Application No.WO2009135070A1 (hereby incorporated by reference), wherein gasconcentration changes in a catheter-isolated lung portion allowcollateral ventilation to be determined.

Quantifying collateral ventilation via collateral resistance measurementand calculations typically takes about two to five minutes. During thistime, the physician must ensure the patient is tolerating sedation,manage secretions to prevent occlusion within the catheter lumen, andmaintain balloon seal/position within the target airway. Any one ofthese factors may extend the assessment time and compromise theassessment results. Thus, there is a need to quantify the magnitude ofcollateral ventilation within a lung compartment (lobe, segment,sub-segment, or the like) more quickly and efficiently.

Another unmet need is a simple and accurate method for determining theperfusion status of a lung segment (i.e., how well a lung segment isbeing supplied with blood). The current gold standard for determiningperfusion status is using ventilation/perfusion scintigraphy (Wang S Cet al. Perfusion scintigraphy in the evaluation for lung volumereduction surgery: correlation with clinical outcome. Radiology. 1997October; 205(1): 243-8). This method requires the use of a gamma camerafollowing the injection of radioactive microspheres. This scanningtechnique is highly sensitive for detection of regional abnormalities ofblood flow and is primarily used for the diagnosis of pulmonaryembolism. It has also been tried in lung volume reduction surgery; thegoal is to determine what regions of the lung are non-functional basedon a mismatch of ventilation and perfusion. Though promising, theaccuracy and application of ventilation/perfusion scintigraphy has yetto be proven due to lackluster results in its application to lung volumereduction surgery. Further, the dyes and separate scanning machinerynecessary for scintigraphy means that this system is both complicatedand costly to use.

It would also be desirable to measure oxygen absorption within the lung,since this could be indicative of the functionality of the lung.Diseased lung portions presumably would not absorb oxygen in the bloodstream as well as non-diseased portions. It would thus be desirable toprovide a method for assessing and comparing oxygen absorption betweenthe various lung segments.

Yet another unmet need in diagnostics is the determination of how well atarget lobe is ventilating. If the target lobe is not ventilating wellas compared to other lobes, then a viable treatment option would be toisolate the lobe via Endoscopic Lung Volume Reduction (ELVR) to allowbetter ventilating lobes to utilize the same space and thereby increasethe overall efficiency of the lung. In case the lobe has collateralventilation (CV positive) and does not ventilate well, the treatment mayconstitute closing off the lobe using ELVR (e.g., endobronchial valves).ELVR then becomes a method to divert airflow to lobes with betterventilation and perfusion rather than a means to reduce lobe size.

If the target lobe ventilates well, then one may not want to isolate thelobe with valves, even if other disease parameters are present in thatlobe. For example, if a lobe does not have collateral ventilation (CVnegative) but still ventilates well, one may not want to close off thelobe using ELVR. One measurable parameter that can determine how well alobe is ventilating is tidal expiratory and/or inspiratory flow. Onecould also monitor other parameters that may correlate to lobe functionincluding airway resistance and pressures, such as the perfusionefficiency of blood in the capillaries of the alveoli.

There is also a need to determine abnormalities in gas exchange/bloodflow to aid with targeting of lobes for endoscopic lung volume reductionin real-time. If the segment/lobe has collateral ventilation, aphysician may still want to treat the lobe if the gas exchange issub-optimal. Ultimately, such a method would enable physicians to treatboth heterogeneous and homogeneous patients using EBVs or otherpulmonary implants that cause lung collapse.

Therefore, it would be advantageous to have new diagnostic techniquesfor evaluating the state of lung disease progression, such asdetermining the presence and degree of collateral ventilation, theviability of lung tissue using parameters such as blood flow and oxygenpermeation, as well as ranking a lung portion for severity of diseaseusing a function of the diagnostic parameters. At least some of theseobjectives will be met by the embodiments described herein.

SUMMARY OF THE INVENTION

This application discloses methods and systems for targeting, accessingand diagnosing diseased lung compartments. In one aspect, a method ofdetermining collateral ventilation in a patient comprises introducing adiagnostic catheter with an occluding member at its distal end into alung segment via an assisted ventilation device, inflating the occludingmember to isolate the lung segment, and performing a diagnosticprocedure with the catheter while the patient is ventilated via theassisted ventilation device. The proximal end of the diagnostic catheteris configured to be attached to a console, and data from the diagnosticprocedure may be displayed on the console. In one embodiment, thediagnostic procedure comprises determining one or more characteristicsof respiration such as flow rate, pressure, or resistance. Thecharacteristics may be used, for example, to determine the presence ofcollateral ventilation. In one embodiment, the assisted ventilationdevice may include a ventilation mask.

In another aspect, a method of assessing the functionality of a lungsegment in a patient comprises introducing a diagnostic catheter with anoccluding member at its distal end into the lung segment, inflating theoccluding member to isolate the lung segment, and monitoring bloodoxygen saturation of the patient. The proximal end of the diagnosticcatheter is configured to be attached to a console, and in someembodiments the method may involve viewing data on the console relatedto the lung segment being assessed. The monitoring step may comprisemonitoring oxygen saturation before and after the inflating step. Afterthe monitoring step, the occluding member may be deflated. Oxygensaturation may be further monitored after deflating the occludingmember. Oxygen saturation may be monitored by a pulse oximeter.

In yet another aspect, a method of assessing the functionality of a lungsegment of a patient comprises introducing a diagnostic catheter with anoccluding member at its distal end into the lung segment, determiningtidal flow volume in the lung segment, determining total lung capacityof the patient, and determining a flow rank value based on the tidalflow volume of the lung segment and the total lung capacity. Theproximal end of the diagnostic catheter is configured to be attached toa console, and at least the tidal volume and total lung capacity aretypically displayed on the console. In one embodiment a treatment optionis determined based on the flow rank value. The occluding member may beinflated to isolate the lung segment.

The method may further comprise determining the presence of collateralventilation in the lung segment and a treatment option may be determinedbased on the presence of collateral ventilation.

Further aspects and embodiments of the present invention are describedin further detail below, in reference to the attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention has other advantages and features which will be morereadily apparent from the following detailed description of theinvention and the appended claims, when taken in conjunction with theaccompanying drawings, in which:

FIG. 1 shows a diagnostic or assessment catheter used in the disclosedmethods according to some embodiments of the present invention.

FIG. 2 shows the placement of the catheter shown in FIG. 1 in the lung.

FIG. 3 shows a console configured to receive the catheter shown in FIG.1 .

FIG. 4 is a flow diagram illustrating one embodiment of the presentinvention.

FIGS. 5A-5C show an example of results obtained by using the methodillustrated in FIG. 4 .

FIG. 6 is a flow diagram illustrating another embodiment of the presentinvention.

FIG. 7 shows results obtained by using the catheter shown in FIG. 1 .

FIG. 8 is a flow diagram illustrating another embodiment of the presentinvention using the results obtained in FIG. 7 .

FIG. 9 is a flow diagram illustrating another embodiment of the presentinvention using the results obtained in FIG. 7 .

FIG. 10 is a chart showing results obtained by using the methods shownin FIGS. 8 and 9 .

FIG. 11 is a chart showing results obtained by using the methods shownin FIGS. 8 and 9 .

DETAILED DESCRIPTION

Although the detailed description contains many specifics, these shouldnot be construed as limiting the scope of the invention but merely asillustrating different examples and aspects of the invention. Variousmodifications, changes and variations may be made in the disclosedembodiments without departing from the spirit and scope of theinvention.

The present application provides methods and systems for targeting,accessing and diagnosing diseased lung compartments. Such compartmentscould be an entire lobe, a segment, a sub-segment or any such portion ofthe lung. Diagnosis is achieved in the disclosed embodiments byisolating a lung compartment to obtain various measurements to determinelung functionality. Though COPD is mentioned as an example, theapplicability of these methods for treatment and diagnosis is notlimited to COPD, but can be applicable to any lung disease.

The methods are minimally invasive in the sense that the requiredinstruments are introduced through the mouth, a tracheostomy, or othersite, typically via a bronchoscope, assisted ventilation device, orother non-surgical device passed through the mouth into the trachea andairways. In some embodiments, the patient is allowed to breathe normallyduring the procedures. Some embodiments may be used with assisted (orpositive pressure) ventilation. The methods involve detecting thepresence or characteristics (e.g., concentration or pressure) of one ormore naturally occurring or introduced gases to determine the presenceof collateral ventilation and/or to measure one or more othercharacteristics of a target lung compartment, such as oxygen saturationof tissue.

In some of the present embodiments, isolation of the lung comprisessealingly engaging a distal end of a catheter in an airway feeding alung compartment, as shown in FIGS. 1 and 2 . Such a catheter has beendisclosed in co-pending published U.S. patent application Ser. No.10/241,733, which is incorporated herein by reference. As shown in FIG.1 , the catheter 100 comprises a catheter body 110, and an expandableoccluding member 120 on the catheter body. The catheter body 110 has adistal end 102, a proximal end 101, and at least one lumen 130,extending from a location at or near the distal end to a location at ornear the proximal end.

The proximal end of catheter 100 is configured to be coupled with anexternal control unit (or “console,” not shown), and optionallycomprises an inflation port (not shown). The distal end of catheter 100is adapted to be advanced through a body passageway such as a lungairway. The expandable occluding member 120 is disposed near the distalend of the catheter body and is adapted to be expanded in the airwaywhich feeds the target lung compartment. In one embodiment, theoccluding member 120 is a compliant balloon made of transparentmaterial. The transparent material allows visualization using thebronchoscope through the balloon. The occluding member 120 is inflatablevia a syringe that is configured to be coupled to the inflation port.Optionally, catheter 100 comprises visual markers at the proximal anddistal ends of the balloon to identify the location of the occludingmember 120 within the airway prior to inflation. The occluding member120 material inflates and seals with inflation pressures between 5-20psi to prevent balloon migration within the airway. This inflationpressure also aids the occluding member 120 in maintaining a symmetricalconfiguration within the airway, thereby ensuring that the catheter(which is centered within the occluding member 120) will remain centeredwithin the airway. The occluding member 120 material and attachment arealso configured to minimize longitudinal movement of the occludingmember 120 relative to the catheter body 110 itself. To accommodate thehigher inflation pressure, the occluding member 120 is made of apolyurethane such as Pellethane 80A, but can be made of any materialthat is configured to maintain structural integrity at a high inflationpressure.

Additionally and optionally, catheter 100 further comprises at least onesensor 140 located within or in-line with the lumen 130 for sensingcharacteristics of various gases in air communicated to and from thelung compartment. The sensors may comprise any suitable sensors or anycombination of suitable sensors, and are configured to communicate withcontrol unit 200. Examples of sensors include pressure sensors,temperature sensors, air flow sensors, gas-specific sensors, or othertypes of sensors. As shown in FIG. 1 , the sensors 140 may be locatednear the distal end 102 of the catheter 100. Alternatively, the sensors140 may be located at any one or more points along the catheter 100, orin-line with the catheter 100 and within the control unit with one ormore measuring components.

As shown in FIG. 2 , at least a distal portion of the catheter body 110is adapted to be advanced into and through the trachea (T). The cathetermay optionally be introduced through or over an introducing device suchas a bronchoscope. The distal end 102 of the catheter body 110 can thenbe directed to a lung lobe (LL) to reach an airway (AW) which feeds atarget lung compartment (TLC), which is to be assessed. When theoccluding member 120 is expanded in the airway, the correspondingcompartment is isolated with access to and from the compartment providedthrough the lumen 130.

The proximal end of the catheter 100 is configured to be coupled with acontrol unit (or “console”) 200, as shown in FIG. 3 . The control unit200 comprises one or more measuring components (not shown) to measurelung functionality. The measuring components may take many forms and mayperform a variety of functions. For example, the components may includea pulmonary mechanics unit, a physiological testing unit, a gas dilutionunit, an imaging unit, a mapping unit, a treatment unit, a pulseoximetry unit or any other suitable unit. The components may be disposedwithin the control unit 200, or may be attached to the unit 200 from anexternal source. The control unit 200 comprises an interface forreceiving input from a user and a display screen 210. The display-screen210 will optionally be a touch-sensitive screen, and may display presetvalues. Optionally, the user will input information into the controlunit 200 via a touch-sensitive screen mechanism. Additionally andoptionally, the control unit 200 may be associated with external displaydevices such as printers or chart recorders. At least some of the abovesystem embodiments will be utilized in the methods described below.

CV Assessment in Ventilated Patients. One embodiment includes a methodof assessing collateral ventilation in a lung of a patient under anassisted breathing arrangement such as a ventilation mask. In thisembodiment, the method involves placing an assisted breathing device,for example the ventilation mask, over the patient's mouth. The catheter100 is introduced into the lung via a viewing scope, which is in turnintroduced into the oral opening of the ventilation mask. Once thecatheter has been introduced to the TLC, the TLC is isolated byinflating the occluding member 120. The flow and pressure variations inthe isolated lung compartment are then measured while the patient isallowed to breathe under a positive pressure through the ventilationmask. In the absence of collateral channels in a normal lung, expiratoryflow from the isolated TLC continuously decreases over several cycles ofrespiration. In the presence of collateral channels connected to theTLC, there is little or no drop in expiratory flow after isolation ofthe TLC, which is used to measure the nature and degree of collateralventilation.

The specific steps involved in this method are shown in greater detailin the flow diagram of FIG. 4 . In step 401, a bronchoscope is insertedinto a patient lung through the ventilator mask. Thereafter, in step402, the bronchoscope is used to observe the lung and identify a targetsegment or lobe of interest. In step 403, the endobronchial diagnosticcatheter 100 is inserted into the airway leading to the lung compartmentof interest, and the occluding member 120 is inflated to isolate thetarget lung compartment. Using console 200, the expiratory flowwaveforms are then recorded in step 404 for a few cycles of respiration,which may last less than a minute. Thereafter, in step 405, theocclusion balloon is deflated and the diagnostic catheter 100 moved toanother lung compartment for another measurement. The procedure may berepeated for several other lung compartments.

The data is then analyzed to obtain information on the collateralventilation status of each of the compartments analyzed. Analysis ofrespiratory waveforms in normal subjects and patients under ventilationis shown in FIGS. 5A-5C. FIG. 5A shows the variation of respiratory flowand pressure over several breath cycles in a normal lung (i.e., one notsubject to collateral ventilation) when no ventilator is used. Afterocclusion, as indicated by the first vertical line, expiratory flowcontinuously decreases to a baseline that is roughly equal to zero.Further, negative pressure is also detected, and as shown, roughlyincreases with the duration of the occlusion.

In contrast, FIGS. 5B and 5C show the results of usingventilator-applied positive pressure on a diseased lung segment (i.e.,one subject to collateral ventilation). The ventilator creates positivepressure, which is applied relatively uniformly across the lung. Thispushes air through adjacent segments/lobes, including through thecollateral channels, and ultimately into the catheter 100. As isapparent in FIG. 5B, the net positive pressure does not allow the flowrate to descend to the zero baseline as occurred in FIG. 5A. Instead, anew flow baseline is established. Further, negative pressure, which wasapparent in 5A, is not detected until after the occlusion is removed (asshown in FIG. 5C).

Using the above methods, collateral ventilation can be quantified in anyof the following ways:

A. The average expiratory air flow volume versus time can be measured.An increase in volume is indicative of greater collateral ventilation.

B. The average maximum air flow magnitude can also be measured. Anincrease in maximum air flow magnitude is indicative of greatercollateral ventilation.

C. An increase in the baseline value for flow could be measured. Anincrease in baseline flow value is indicative of greater collateralventilation.

D. The average change (delta) between flow baseline and the standardzero value could be measured. A greater average change is indicative ofgreater collateral ventilation.

E. Alternatively, the physician could decrease or increase the amount ofpositive pressure during the assessment period. The drop or rise in flowbaseline as a result of the change in positive pressure, respectively,may be correlated to the magnitude of collateral ventilation.

In each of the above circumstances, an additional method may optionallybe used to normalize flow data recorded from a particular lobe/segmentdue to differences in lobe/segmental volumes and airway resistances.

The primary advantage of this method is the rapid determination of thepresence of collateral flow—often in less than a minute of assessmentunder ventilation, while other previously known methods require at least2-5 minutes of measurement. The method also provides for more accuratedetermination of the degree of collateral ventilation, as a singlemeasurement provides sufficient data to obtain several differentparameters relating to collateral flow as detailed above.

Another advantage of this method is that since it applies positivepressure, it may also open hidden collateral channels that are closeddue to a layer of secretions. These collateral channels may not be openfor study using methods that do not use such positive pressure.Ventilator based assessment may thus forcibly open these occludedchannels and provide detection of these hidden collateral pathways.

Method of Assessing Health of a Lobe Using Oxygen Saturation. Anothermethod of improved diagnosis is a method of assessing abnormalities ingas exchange/blood flow within a target lung compartment using the levelof oxygen perfusion. Specifically, a TLC is isolated while the overalloxygen saturation of the blood is monitored using a pulse oximeter. Achange in the overall oxygen saturation of the blood indicates the levelof functioning of the lobe.

This method is described in further detail in the flow diagram in FIG. 6. As shown in FIG. 6 , in the first step 601, a bronchoscope is insertedinto a patient's lung and a TLC is identified. Catheter 100 is thenintroduced in step 602 through the working channel of the bronchoscopeand positioned within the airway leading to the TLC. At this location, apulse oximeter is used to measure oxygen saturation of the tissues instep 603 to provide a baseline value. The TLC is then isolated byinflating the occlusion element (604), and oxygen saturation iscontinuously recorded by the oximeter until a new equilibrium level isreached (605). The balloon is then deflated and post-deflation, theoxygen saturation is again continuously recorded till the originalbaseline is reached again (606). The process is repeated for alllobes/segments of interest (607).

The oxygen saturation data may be used in any of several ways todetermine the perfusion efficiency of the TLC:

-   -   A. The rate at which oxygen concentration decreases (slope of        oxygen saturation versus time) once TLC is isolated is        correlated to the percentage the targeted lobe contributes to        the overall perfusion of the lung.    -   B. The rate at which oxygen concentration increases (slope of        oxygen saturation versus time) once the isolation is ceased is        correlated to the percentage the targeted lobe contributes to        the overall perfusion of the lung.    -   C. The difference in oxygen saturation between pre-isolation and        post-isolation is also correlated to the percentage the TLC        contributes to the overall perfusion of the lung.    -   D. Based on the oxygen saturation data received from all lobes,        the rate of change in saturation is compared and normalized to        adjust for differences in volumes of different lung        compartments.    -   E. Furthermore, using console 200, flow rate is optionally        recorded to quantify ventilation from each lobe. The ventilation        data is then optionally used to calculate ventilation and        perfusion and potentially determine mismatches between        ventilation and perfusion in real-time.

In practice, as the oxygen saturation is constantly in flux based on thedegree of sedation, breath rate, position of bronchoscope, secretionstatus, and other factors, it is important that the above assessment isdone fairly quickly to minimize the effects of these other factors onthe results. In addition, the oximeter needs to have a sufficiently fineresolution to detect a drop in oxygen saturation due to occlusion. Thepulse oximeter may be connected directly to the console 200 forcontinuous monitoring and recording of oxygen saturation data.

Degree of Oxygen Absorption. In a related embodiment, the degree ofoxygen absorption in various lung lobes can be determined in order todetermine lung functionality. In this situation, the patient is givensupplemental oxygen. The oxygen concentration is then measured in aportion of the bronchial tree where there is no gas exchange (e.g., in aprelobar segment of the bronchus). The oxygen is then measured invarious segments downstream of the first measurement. The values arethen compared. Segments with poor function will exhibit values similaror closer to the first measurement. Those segments that exhibit valuessimilar or closer to the first measurement (at portion with no gasexchange) are presumed to have decreased functionality.

Method of Assessing the Health of a Lung Compartment Using Flow Ranking.Another method disclosed in the present application is a method ofassessing the health of a lung compartment by determining the ability ofthe compartment to ventilate. A poorly ventilating lobe provides reducedfunctional benefit to the patient's overall lung function and is thusconsidered an encumbrance to the rest of the lung. If the target lobe isnot ventilating well in comparison to other lobes, the lobe can beisolated via endoscopic lung volume reduction (ELVR) to allow betterventilating lobes to utilize the same space and thereby increase theoverall efficiency of the lung.

The method thus involves ranking various segments on the basis of thepresence and degree of collateral ventilation within the segment and thesegment's ventilation status, as determined by the expiratory and/orinspiratory flow, airway resistance and pressures. The ranking data isthen used to determine the course of treatment, which may includeplacing a one-way valve.

For example, if the target segment ventilates well, then one may notwant to isolate the lobe with valves. This may be true even when asegment has no collateral ventilation (CV negative), which wouldordinarily have subject it to treatment using an EBV. If such a segmentventilates well, it may still be useful to the functioning of the lungas a whole and a user may choose to not isolate it. Similarly, if asegment has collateral ventilation (CV positive), it would not beindication for treatment with valves. However, if such a segment did notventilate well, it may indicate that the lobe would benefit from ELVR(e.g., endobronchial valves). ELVR thus becomes a method to divertairflow to lobes with higher perfusion and ventilation rates rather thanexclusively a means to reduce lobe size.

The ventilation status of a lung compartment is measured using the samecatheter and method of using a catheter that was shown in FIGS. 1-3 .The assessment catheter 100 is introduced into a TLC in a patient.Occluding member 120 is then inflated to isolate the target lungcompartment. Characteristics of the air flowing into and out of the TLCare then measured. A result is shown in FIG. 7 , where the respiratoryflow into and out of the target lung compartment is shown as a functionof time. Regular air flow is measured as shown to the left of the linemarked “CV assessment”. The average tidal flow volume (ATFV) isdetermined by calculating the average flow rate over the course of a fewbreath cycles. In this case, the ATFV is determined by looking at theaverage tidal expiratory volume (ATEV) over the course of three cycles.

Then, when CV assessment begins, the TLC is isolated, resulting in thewave form shown to the left of the line marked “CV assessment”. Thevolume of air expired decreases gradually over time. This indicates anabsence of collateral ventilation, since the isolated lung compartmentis apparently not receiving inflow even though expiratory flow takesplace. The expiratory air flow shown is thus obtained from a normal lungcompartment with no collateral ventilation (CV negative).

After sufficient measurements are obtained as shown above, the course oftreatment to be followed is determined using a flow ranking parameterand is illustrated in FIG. 9 . Flow rank is defined by the relation:

Flow Rank=ATEV (ml)/TLV (liters)*10, where ATEV—is the average tidalflow volume in ml and TLV—the total lung capacity (volume) in liters.Both ATEV and TLV are values obtained from the console 200. Themultiplier 10 is added to obtain a convenient numerical value.

Further, if necessary, ATEV may be calculated as follows:

ATEV=TTEV/number of cycles, where TTEV is the total tidal expiratoryvolume during the given number of cycles.

Both collateral ventilation values and flow rank values for each segmentmeasured are compared to values obtained from the general population,other lobes within the patient, or the same segment within the patientover the course of time. For the purposes of providing an example, aflow rank (FR) value greater than 15 is deemed to indicate a segmentthat ventilates well, and a FR value less than 5 is deemed to indicate asegment that ventilates poorly.

Using such parameters, a proposed method for determining the course oftreatment using both collateral flow characteristics and Flow Ranking isshown in FIG. 8 . As shown by option A, when the target lobe does notshow collateral ventilation (CV negative), but ventilates less thanoptimally (FR<15), the lobe is treated by placing a valve. However, asshown in case B, if the lobe is CV− but ventilates very well (FR>15),valve placement is not recommended. If collateral ventilation isstrongly present, as in case C, regardless of ventilation status, valveplacement is presumed to not significantly influence gas exchange and isnot recommended. If, as in case D, a lobe has weak collateralventilation and does not ventilate well (FR<5), valve placement isrecommended, in which case ELVR becomes a method to divert airflow tolobes with higher perfusion and ventilation capabilities, rather than ameans to reduce lobe size. If, however, as in case E, the target lobestill shows the ability to ventilate (FR>5), then the lobe is notisolated with valves.

An example of Flow Rank calculation and treatment using the above schemeis shown below, where the average tidal expiratory volume is calculatedbased on three expiratory cycles. As an example, the values obtainedfrom the graph shown in FIG. 7 are used:

-   -   Total Tidal Expiratory Volume (TTEV) over 3 samples (Based on        Assessment Displayed in FIG. 7 )=42.15 mL and Average Tidal        Expiratory Volume (ATEV)=TTEV/3=42.15/3=14.05 mL.    -   Patient's Total Lung Capacity=5.78 liters.    -   Flow Rank=ATEV (ml)/TLC (liters)*10=(14.05/5.78)*10=24.3.    -   Based on the Assessment shown in FIG. 7 , Lobe is CV− but F.R.        of 24.3>=15.    -   Valve Placement Not Recommended.

Optionally, treatment options can also be determined without assessmentof collateral ventilation, e.g., using Flow Ranking alone, as shown inFIG. 9 , in which case the decision to place a valve is based on whetherthe ventilation status is poor (place valve) or good (do not placevalve).

Additionally or optionally, the method of the invention may adopt abaseline flow rate to eliminate patient-to-patient variability. Such asbaseline may be obtained by normalizing the flow data with the overalltotal lung capacity or other lobe/lung volume data. Another solution maybe to normalize the values for the target lobes against unaffected orhealthy lobes within the same patient to determine the target lobe'sproportional output.

Additionally or optionally, other parameters can be measured by console200 which could also be predictors, such as airway resistance (hightidal resistance=poor ventilating lobe), pressure (low tidalpressure=poor ventilating lobe) and oxygen perfusion efficiency. Theinclusion of one or more of the above parameters may provide a bettermethod of ranking overall lobe function (based on resistance, pressure,flow and perfusion) as well as utilizing CV assessment data to guideELVR therapy decisions.

Clinical Data. The effect of treatments using the five options in FIG. 8was studied in a clinical setting, and the results are shown in FIGS. 10and 11 . FIG. 10 represents data for patients who received a valve. FIG.11 represents data for patients who did not receive a valve. Thepatients in both cases were assessed under three parameters—a) SGRQ (St.George's Respiratory Questionnaire), b) FEV1 (ratio of forced expiratoryvolume in 1 second to forced vital capacity), and c) 6MWT (6 minute walktest). The change between baseline (pre valve-placement) and post-30 dayfollow up values were determined in patients treated using the severaloptions.

Some results for patients implanted with a valve are shown in FIG. 10 .The chart reflects data collected for patients:

-   -   Who Received Emphasys Valves;    -   With Atelectasis of the Target Lobe;    -   For Whom the Collateral Ventilation Assessment Measured        CV-negative;    -   For Whom the Flow Rank with Collateral Ventilation Assessment        diagnostic algorithm recommends a valve; and    -   For Whom the Flow Rank without CV assessment recommends a valve.

Some results for patients implanted with a valve are shown in FIG. 11 .The chart reflects data collected for patients:

-   -   With no Atelectasis in Target Lobe; For Whom Collateral        Ventilation Assessment Measured CV-positive in Target Lobe;    -   For Whom the Flow Rank with Collateral Ventilation Assessment        diagnostic algorithm does not recommend a valve; and    -   For Whom the Flow Rank without CV assessment does not recommend        a valve.

As observed in FIGS. 10 and 11 , among all the methods of screeningpatients, Flow Ranking both with and without CV assessment appears toidentify those patients who would benefit from ELVR therapy mostoptimally, as the positive values of test parameters are highest forthese two categories of patients.

The flow ranking measurement and algorithm potentially opens treatmentoptions to both heterogeneous and homogeneous emphysema patients andoffers an opportunity to screen homogeneous emphysema patients with lowflow rank.

Although certain embodiments of the disclosure have been described indetail, certain variations and modifications will be apparent to thoseskilled in the art, including embodiments that do not provide all thefeatures and benefits described herein. It will be understood by thoseskilled in the art that the present disclosure extends beyond thespecifically disclosed embodiments to other alternative or additionalembodiments and/or uses and obvious modifications and equivalentsthereof. In addition, while a number of variations have been shown anddescribed in varying detail, other modifications, which are within thescope of the present disclosure, will be readily apparent to those ofskill in the art based upon this disclosure. It is also contemplatedthat various combinations or subcombinations of the specific featuresand aspects of the embodiments may be made and still fall within thescope of the present disclosure. Accordingly, it should be understoodthat various features and aspects of the disclosed embodiments can becombined with or substituted for one another in order to form varyingmodes of the present disclosure. Thus, it is intended that the scope ofthe present disclosure herein disclosed should not be limited by theparticular disclosed embodiments described above. For all of theembodiments described above, the steps of any methods need not beperformed sequentially.

What is claimed is:
 1. A method of assessing the functionality of a lungsegment in a patient, the method comprising: introducing a diagnosticcatheter into the lung segment, wherein the diagnostic cathetercomprises a distal end comprising an occluding member and a proximal endconfigured to be attached to a console; inflating the occluding memberto isolate the lung segment; monitoring blood oxygen saturation of thepatient; and determining functionality of the lung segment based on arate of change of blood oxygen concentration.
 2. The method of claim 1,wherein the monitoring step comprises monitoring oxygen saturationbefore and after the inflating step.
 3. The method of claim 1, furthercomprising deflating the occluding member after the monitoring step. 4.The method of claim 3, further comprising monitoring oxygen saturationafter the deflating step.
 5. The method of claim 1, wherein themonitoring step is conducted by a pulse oximeter.